Many mouse chromosomal genes are known which affect the susceptibility of mice to retrovirus-induced neoplastic disease. These genes include endogenous retroviral sequences, mouse cellular genes which facilitate or restrict virus replication, and proto-oncogenes disrupted by viral insertion. We have been using standard classical genetics to identify and map genes involved in these phenomena. In one series of experiments, we obtained a molecular clone of the receptor for the amphotropic MuLV cell surface receptor, and we defined the map location of this gene in the mouse. We have also mapped TRBP, a positive regulator of HIV-1, in man and mouse. In other experiments, we have continued analysis of several crosses involving DBA/2J mice which carry a locus, Rmcf, responsible for resistance to the mink cell focus inducing (MCF) subtype of mouse leukemia viruses. We defined the genetic map location of Rmcf; we identified an additional resistance gene in the M. castaneus parent of these same crosses which maps to Chr 1; we identified two additional factors which contribute to this resistance in M. castaneus; and we are following inheritance of Rmcf in serial backcrosses to M. castaneus which lacks endogenous MCF viruses. These experiments should help determine whether Rmcf represents an endogenous provirus, expression of which blocks viral cell surface receptors, and should characterize the genetic factors responsible for resistance in M. castaneus.